Preparation and application of 2-(1H-pyrazol-3-yl)pyridine_Industrial additives

Preparation and application background and overview of 2-(1H-pyrazol-3-yl)pyridine

2-(1H-pyrazol-3-yl)pyridine is an organic intermediate that can be used to prepare a pyrazolidinol-copper complex. This complex is a mononuclear Cu complex and has anti-tumor activity.

Preparation and application of 2-(1H-pyrazol-3-yl)pyridine

Step 1. Add 40ml DMF-DMA to a 250ml three-necked flask, then add 24.2g 2-acetylpyridine, heat to 126.1~126.3°C, stir and reflux for 16 hours, cool, and concentrate the solution under vacuum to remove the solvent to obtain a crude yellow solid. Product, the yellow solid crude product is recrystallized with CHCl₃-n-hexane. CHCl₃-n-hexane is prepared by volume of CHCl₃ and n-hexane. It was prepared with a ratio of 1:1. After recrystallization, 21.95g of yellow 1-(2-pyridyl)-3-dimethylamino-2-propenone crystals were obtained, with a yield of about 75.7%;

Step 2. Add 17.62g of 1-(2-pyridyl)-3-dimethylamino-2-propenone into a 250ml three-necked flask, then add 20ml of ethanol with a mass concentration of 95%, and stir magnetically For the reaction solution, measure 34 ml of hydrazine hydrate with a mass concentration of 85% and add it to 10 ml of ethanol with a mass concentration of 95% and mix well. After mixing, add dropwise to the reaction solution using a constant pressure dropping funnel. , after the dropwise addition is completed, heat to 121.8-122.1°C and reflux for 1 hour, distill under reduced pressure and concentrate until the volume of the reaction solution is 9-11 ml, then add 100 ml of distilled water, cool overnight, a white precipitate will precipitate, filter with suction, and dry to obtain a white solid crude product. The white solid crude product was recrystallized with acetone. After recrystallization, 9.06g of 2-(1H-pyrazol-3-yl)pyridine white crystals were obtained, with a yield of about 62.4%;

Preparation and application of 2-(1H-pyrazol-3-yl)pyridine

2-(1H-pyrazol-3-yl)pyridine is an organic intermediate that can be used to prepare a pyrazolidinol-copper complex:

1) Add 50ml of toluene and 1g of 2-(1H-pyrazol-3-yl)pyridine into a 250ml three-necked flask, add 10ml of NaOH solution with a mass concentration of 28 to 30% and a mass concentration of 28 to 30% under magnetic stirring. 10% n-Bu₄NOH solution 1ml, heated to 69~72℃ and refluxed for 1.5h, then add 0.85g of 1,3-dichloro-2-propanol dropwise, 69~72℃ Continue to reflux for 45 hours, cool to room temperature, separate the magnesium carbonate mechanical phase, rinse the solid phase with water, and then extract with CHCl₃. After the extraction is completed, remove CHCl₃ under vacuum conditions. The crude product is obtained, and the crude product is recrystallized with CHCl₃-n-hexane. CHCl₃-n-hexane is reacted with CHCl₃ and n-hexane. It was prepared with a volume ratio of 1:1. After recrystallization, 1.74g of colorless needle-like crystals of 1,3-bis[3-(2-pyridine)pyrazole]-2-propanol was obtained, with a yield of approximately 73%;

2) Dissolve 0.14g 1,3-bis[3-(2-pyridine)pyrazole]-2-propanol in 10ml methanol, add 0.016g NaOH under magnetic stirring, stir for 30min, and then drop by drop Add copper bromide-methanol solution. The copper bromide-methanol solution is prepared by dissolving 0.089g copper bromide in 5 ml methanol. Continue stirring the reaction at room temperature for 1 hour, then filter to obtain a green filtrate. The filtrate naturally evaporates at room temperature. Until methyltetrahydrofuran is completely separated from the flaky crystals, a pyrazolidinol-copper complex with the molecular formula CuLBr·4H2O is obtained, in which L is 1,3-bis[3-(2-pyridine)pyrazole]-2-propanol. alcohol.

References

[1][Chinese invention] CN201210242532.7 A pyrazolidinol-copper complex and its preparation method and application